Methylazoxymethanol (MAM) acetate induces adenocarcinoma of the colon in more than 70 percent of rats given a single treatment. This system, in which the time of tumor initiation is known, allows for the sequential study of biochemical and pathologic changes up to the time of tumor development. The sites and incidence of tumor development and the histologic characteristics of the tumors bear a striking similarity to those found in humans. The data suggest, therefore, that this system may serve as a model for studies in colon carcinogenesis. Specifically, studies will be concerned with determining early premalignant changes induced by MAM acetate to establish parameters for early diagnosis of colon cancer. Crypt and surface epithelial cells normally differ in the level of DNA synthetic activity and in the activity of several nucleic acid associated enzymes. Experiments are described to determine whether MAM acetate induces in surface epithelial cells reversion of their DNA and enzyme activities to those of crypt cells. Secondly, the available evidence indicates that colon is more sensitive to chemical carcinogens than is the small intestine. Studies of the rate and extent of repair of carcinogen altered DNA will be carried out comparing various segments of bowel. Both autoradiography and density gradient centrifugation will be used to determine repair synthesis of DNA in replicating and non- replicating cells. Thirdly, MAM acetate induces changes in hepatic nucleoprotein structure and function and such changes will be sought for in colon. Studies as outlined here may provide additional information towards understanding the initiation and development of colon cancer.